1. Technical Field of the Invention
The present invention relates, as novel and useful industrial products, to a novel class of biaromatic compounds that activate the Peroxisome Proliferator-Activated Receptor type receptors of subtype γ (PPARγ). This invention also relates to processes for the preparation of same and to their formulation into pharmaceutical compositions useful in human or veterinary medicine, or, alternatively, into cosmetic compositions.
2. Description of Background and/or Related and/or Prior Art
The activity of receptors of PPAR type has been the subject of numerous studies. See, for example, the publication entitled “Differential Expression of Peroxisome Proliferator-Activated Receptor Subtypes During the Differentiation of Human Keratinocytes”, Michel Rivier et al., J. Invest. Dermatol., 111, 1998, pp. 1116-1121, in which is listed a large number of bibliographic references relating to PPAR type receptors. See also the report entitled “The PPARs: From orphan receptors to Drug Discovery”, Timothy M. Willson, Peter J. Brown, Daniel D. Sternbach, and Brad R. Henke, J. Med. Chem., 2000, Vol. 43, pp. 527-550.
The PPAR receptors activate transcription by binding to DNA sequence elements known as the peroxisome proliferator response elements (PPRE), in the form of a heterodimer with the retinoid X receptors (known as RXRs).
Three subtypes of human PPAR have been identified and described: PPARα, PPARγ and PPARδ (or NUC1).
PPARα is mainly expressed in the liver, whereas PPARδ is ubiquitous.
Of the three subtypes, PPARγ is the one that has been the most extensively studied. All the references suggest a critical role of PPARγ in the regulation of differentiation of adipocytes, where it is strongly expressed. It also plays a key role in systemic lipid homeostasis.
It has especially been described in WO 96/33724 that PPARγ-selective compounds, such as a prostaglandin-J2 or -D2, are potential active agents for the treatment of obesity and diabetes.
Moreover, in WO 02/12210 and WO 03/055867 the assignee hereof describes the formulation of biaromatic compounds that activate PPARγ type receptors into a pharmaceutical composition, the composition being useful for treating skin disorders associated with an anomaly of epidermal cell differentiation.
Need continues to exist for novel compounds that have good activity and advantageous pharmaceutical properties.